Posterior Uveitis

INTRODUCTION

Uveitis comprises a group of diseases characterized by inflammation of the uveal tract, which is composed of the iris, ciliary body, and choroid. These structures comprise the vascular coat of the eye and play many essential roles in the proper functioning of the visual system, such as control of the amount of light entering the eye, aqueous humor formation, accommodation, aqueous outflow, and blood supply to the photoreceptors and outer retina. Uveal inflammation frequently results in visual dysfunction and visual loss. Pharmacotherapy is the mainstay of uveitis treatment and preserves vision by reducing and preventing inflammation, thereby protecting ocular tissues from damage. This chapter discusses the key diagnostic features and pharmacotherapeutic approaches for the management of common posterior uveitis entities.

DISEASE PREVALENCE AND INFLUENCE

Uveitis is a significant cause of ocular morbidity worldwide and affects individuals of all ages and both genders.1–5 The largest study conducted in North America estimated the incidence of uveitis to be 52.4/100 000 person-years and the prevalence to be 115.3/100 000 population.3 Epidemiological data estimate the incidence of chronic, noninfectious posterior uveitis to range from 14 to 17/100 000.5 The economic burden of uveitis and its treatment is likely to be increasingly heavy as young populations mature. A study of Medicare data from elderly patients revealed that, in the 1990s, the cumulative prevalence of uveitis increased from 511/100 000 to 1231/100 000, with anterior uveitis accounting for most cases. The same study estimated the average incidence of posterior uveitis to be 76.6/100 000 and the incidence of panuveitis and endophthalmitis to be 41.7/100 000.6

Uveitis is believed to be the fourth leading cause of blindness among the working population (ages, 20–60 years). Visual impairment has been reported to involve approximately 35–70% of uveitis patients, unilateral visual loss to involve approximately 14–50%, and bilateral visual loss to involve 4–50% of patients.2,6 Uveitis is responsible for many ocular complications, such as cystoid macular edema (CME), cataract, glaucoma, and retinal detachment (RD). The frequency of complications increases with disease duration. In the course of the disease, surgery is performed in about half of all patients.2,7

developing Vogt–Koyanagi–Harada (VKH) disease, while Caucasians are prone to develop BSRC.

The risk factors for visual loss or impairment due to uveitis are varied but the most significant ones include panuveitis, posterior uveitis, bilateral inflammation, duration of disease, delay in presentation to subspecialist, increased patient age, and development of complications (CME, cataract, glaucoma).6,9 In one large series, juvenile rheumatoid arthritis and sarcoidosis were the systemic conditions most associated with visual loss.2

PATHOGENESIS

Inflammation is a protective response of the human body which aims to remove causes of injury such as microbial agents and toxins, as well as byproducts of injury such as damaged and dead cells and tissues. The components of the immune system comprise the main participants in the inflammatory process, including cellular (leukocytes, lymphocytes) and humoral (antibodies, cytokines) elements. Immune system activation produces the classic inflammatory features of warmth, redness, pain, swelling, and malfunction. The underlying processes causing these signs include vasodilation, increased blood flow, extravasation of plasma proteins, emigration of cellular elements from the circulation, secretion of chemical mediators of inflammation (prostaglandins, leukotrienes, nitric oxide, complement factors, histamines, lysozomal enzymes, platelet-activating factors). When inflammation is inappropriately directed or prolonged, damage to the normal body tissues may occur, leading to disease and morbidity.

In most cases of uveitis, permanent visual morbidity does not result from a single episode but from recurrent episodes of inflammation or prolonged disease, which produce cumulative tissue damage. The most common cause of severe visual loss among uveitis patients is CME, which occurs in about half of patients with posterior uveitis.2,9 Other significant causes of visual loss include cataract, glaucoma, RD, and chorioretinal scarring. Onset of these complications and resulting visual outcomes are correlated with the frequency and duration of inflammatory episodes.9,10 In order to preserve as much visual function as possible, the goal of pharmacotherapy for posterior uveitis should be total elimination of inflammation through appropriate and adequate management. Fortunately, the range of available pharmacotherapeutic modalities has expanded such that the vast majority of uveitis conditions are amenable to treatment.

RISK FACTORS

The risk factors for developing a particular kind of uveitis are multifactorial and not fully identified but include genetic, racial, geographic, and environmental factors.8 The association of major histocompatibility haplotypes with particular uveitis entities highlights the importance of genetic factors on development of uveitis. For example, the human leukocyte antigen (HLA)-A29 genotype is associated with birdshot chorioretinopathy (BSRC) while HLA-B51 is associated with Behçet’s disease. Racial or ethnic background also determines risk for developing a particular type of uveitis. For example, Asians are predisposed to

SPECIFIC DISEASES: DIAGNOSIS AND PHARMACOTHERAPY

In this section, we discuss the diagnostic features of common, posteriorsegment inflammatory conditions and discuss currently available treatments. The principles of treatment and therapeutic agents discussed here are applicable to other, less common uveitis entities such as retinal vasculitis, white-dot syndromes, and intermediate uveitis, The pharmacokinetic features and dosages of each drug are discussed in more detail in another section of this book.